Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.

Change in Level of Service Inventory-Ontario Revised (LSI-OR) Risk Scores Over Time: An Examination of Overall Growth Curves and Subscale-Dependent Growth Curves.

The dynamic nature of risk to re-offend is an important issue in the management of offenders and has stimulated extensive research into dynamic risk factors that can alter an individual's overall risk to re-offend if addressed. However, few studies have examined the relative importance of these dynamic risk factors, complicating the task of developing case management and treatment plans that will effect the most change. Using a large, high-risk sample and multi-wave data of a common risk assessment tool, the Level of Service Inventory-Ontario Revised (LSI-OR), the current study investigated the relationship among criminogenic risk factors and their role in influencing the overall risk score. Results indicated a diverse pattern of effects on the eight subscale scores, specifically suggesting that changes on Procriminal Attitude/Orientation, Criminal History, and Leisure/Recreation subscales resulted in a quicker rate of change to the overall risk score over time. These results suggest that some factors may be driving the change in overall risk and could potentially effect the most change if prioritized for intervention. Practical implications and implications for further research are discussed.